QUESTIONS: alpha-helix "signals" in proteins
kenp at banyo
Tue Jul 5 15:12:04 EST 1994
Simon Brocklehurst (Bioc) (smb18 at mole.bio.cam.ac.uk) wrote:
: Ken Prehoda <kenp at nmrfam.wisc.edu> writes:
: >Since protein folding is believed to be thermodynamically controlled
: Errr... NOT!
What is the problem with my statement. The current consensus is
that protein folding is thermodynamically controlled. It is true
there are dissentions from the consensus, but when is that not
the case? If you believe otherwise, please provide references (and
not quotes from Wayne and Garth as you seem to prefer). I refer
you to reviews by Baldwin & Kim, Dill, and many others.
: >(OK, see Agard, et al. for counterviews), this is really irrelevant
: >to what you seem to be getting at. Remember that G is a state function
: >and is therefore independent of path.
: The bottom line is that folding pathway(s) is/are almost certainly
: involved in getting to the _native_ state - so kinetics _are_
: I would bet money that anyone who says different is wrong!
Of course a folding pathway is involved in going from the unfolded
state to the native state. That's a given. Whether or not
the pathway determines the structure is a very different question.
And whether or not you would bet money on it has little to do with
the scientific merits of your position.
: As for the original point about the relatiave importance of secondary
: vs tertiary vs intrinsic interactions, for controlling formation of
: (secondary) structure:
Could you please explain what you mean by "intrinsic" interactions? If
you are refering to the so-called helical-propensity, then how can
you distinguish between secondary, tertiary and intrinsic interactions?
: Why can't they all be "equally" important??? That is, maybe in
: one bit of a protein, intrinsic preferences are crucial for
: driving structure formation, whereas in a different bit, secondary
: interactions could be dominant.
: If this was true, then there would be different percentages
: of residues whose conformation was mainly determined by one of
: the above "things". What these numbers would be is anyone's guess.
: But, it is worth remembering that the so-called "hydrophobic effect"
: is most likely to be the major driving force in structure formation.
Depending on your definition of the hydrophobic effect, this is highly
debatable (well it is debatable regardless of your definition, but
without knowing what you mean by the hydrophobic effect I cannot
argue the point).
: In the simplest model for considering this effect, there need be no
: difference between secondary and tertiary interactions when considering
: this "effect".
: My guess is that, on average, secondary and tertiary interactions of
: residues dominate over "intrinsic" residue preferences" in driving the
: formation of secondary structure.
: | ,_ o Simon M. Brocklehurst,
: | / //\, Oxford Centre for Molecular Sciences,
: | \>> | Department of Biochemistry, University of Oxford,
: | \\, Oxford, UK.
: | E-mail: smb at bioch.ox.ac.uk
kenp at nmrfam.wisc.edu
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